The terrorist attacks of 2001 involving anthrax underscore the imperative that safe and effective medical countermeasures should be readily available. Vaccination appears to be the most effective form of mass protection against a biological attack, but the current vaccines have drawbacks that justify the enormous amount of effort currently being put into developing more effective vaccines and other treatment modalities. After providing a comprehensive overview of the organism Bacillus anthracis as a biological weapon and its pathogenicity, this review briefly summarizes the current knowledge vital to the management of anthrax disease. This knowledge has been acquired since 2001 as a result of the progress on anthrax research and focuses on the possible development of improved human anti-infective strategies targeting B. anthracis spore components, as well as strategies based on host–pathogen interactions.